4-(3,4-dihydro-1H-isoquinolin-2yl)-pyridines and 4-(3,4-dihydro-1H-isoquinolin-2-yl)-quinolines as potent NR1/2B subtype selective NMDA receptor antagonists

Bernd Büttelmann; Alexander Alanine; Anne Bourson; Ramanjit Gill; Marie-Paule Heitz; Vincent Mutel; Emmanuel Pinard; Gerhard Trube; René Wyler

doi:10.1016/s0960-894x(03)00232-4

4-(3,4-dihydro-1H-isoquinolin-2yl)-pyridines and 4-(3,4-dihydro-1H-isoquinolin-2-yl)-quinolines as potent NR1/2B subtype selective NMDA receptor antagonists

Bioorg Med Chem Lett. 2003 May 19;13(10):1759-62. doi: 10.1016/s0960-894x(03)00232-4.

Authors

Bernd Büttelmann¹, Alexander Alanine, Anne Bourson, Ramanjit Gill, Marie-Paule Heitz, Vincent Mutel, Emmanuel Pinard, Gerhard Trube, René Wyler

Affiliation

¹ Pharma Division, Discovery Chemistry, F. Hoffmann-La Roche Ltd., CH-4070 Basel, Switzerland. [email protected]

PMID: 12729659
DOI: 10.1016/s0960-894x(03)00232-4

Abstract

A series of 4-(3,4-dihydro-1H-isoquinolin-2yl)-pyridines and analogous quinolines was prepared and evaluated as NR1/2B subtype selective NMDA receptor antagonists. 2-Hydroxyalkylamino substitution combines high affinity with selectivity (vs alpha1 and M1 receptors) and activity in vivo.

MeSH terms

Animals
Mice
Pyridines / chemical synthesis*
Pyridines / pharmacology
Quinolines / chemical synthesis*
Quinolines / pharmacology
Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
Seizures / drug therapy
Structure-Activity Relationship

Substances

NR1 NMDA receptor
NR2B NMDA receptor
Pyridines
Quinolines
Receptors, N-Methyl-D-Aspartate